Date of Award

Winter 12-22-2021

Degree Type


Degree Name

Doctor of Philosophy (PhD)




Chisholm, John D

Second Advisor

Erdman, Scott E.

Subject Categories

Chemistry | Physical Sciences and Mathematics


Mono-O-alkylated 1,1′-bi-2-naphthols (BINOLs) are often used as the source of chirality for catalysts or ligand systems that are employed in asymmetric organic transformations. However, these BINOLs can be hard to synthesize. The O-alkylation of BINOL can be accomplished with primary and secondary alkyl halides or under Mitsunobu conditions, the yields of these alkylations with tertiary halides or alcohols are very low. A new protocol was developed utilizing trichloroacetamide electrophiles to install bulky groups onto one of the phenolic oxygens. Trichloroacetimidates are also shown to be useful reactions for the synthesis of esters. These reagents proceeded through a symbiotic activation pathway. Under these conditions sensitive substrates did not decompose, which often is observed with other conditions using Lewis or Brønsted acids. These reactions have been broadened to benzyl esters without electron donating groups on the benzylic ring. The trichloroacetimidates therefore provide inexpensive and convenient methods that should find use in the formation of esters in complex substrates. Benzylic amines are important structural features in pharmaceuticals, food additives, and insecticides. Many methods to synthesize benzylic amines have been developed but many of these protocols generate significant waste by-products. Additionally, the benzylic amines are often protected as amides or carbamates in a second step, which requires further resources and produces more waste. Alternatively, the rearrangement of benzylic trichloroacetimidates to acetamides may provide direct access to protected benzylic amine containing systems in a single step. The activity of palladium catalysts in the rearrangement of benzylic trichloroacetimidates to acetamides was explored. Using tris(dibenzylideneacetone)dipalladium(0) gave promising results. The exploration of chiral ligands to access enantioenriched products from this reaction has been investigated. N-Alkylated pyrazoles and benzotriazoles are present in a number of natural products and pharmaceuticals. However, methods of synthesizing pyrazoles and benzotriazoles generally use hydrazine derivatives and limited regioselectivity. N-Alkylated pyrazole utilizing trichloroacetimidate electrophiles under Bronsted acid catalyzed conditions has been developed. Both primary and secondary imidates provided good yields. Benzylic primary imidates provided significantly better yields than phthalimidomethyl imidate. Structurally different pyrazoles were also studied in this transformation. Changing the halogen was tolerated, however, iodine provided the lowest yield. When adding methyl groups at the 3 and 5 position on the pyrazole, product was isolated in moderate yield. Interestingly, when using benzotriazole, a single product was isolated in good yield. This was the dearomatized alkylated product. Further substrate scope investigations and mechanism studies need to be performed to better understand these results. Oxoammonium salts are commonly used to oxidize alcohols to aldehydes or ketones, but these reagents may also be used in a number of other oxidative transformations which are useful in organic chemistry. Taking advantage of these reagents, a new tandem elimination-oxidation process of tertiary alcohols has been discovered, synthesizing a protected allylic alcohol. Data suggests that the transformation first proceeds through elimination of the alcohol mediated by the oxoammonium salt. Then the allylic oxidation proceeds through an ene type mechanism. Additionally, the tetramethylpiperidine derived from the oxoammonium salt also serves as a protecting group for the newly generated allylic alcohol, resulting in a process with high atom economy. The optimization and scope of the reaction has been investigated. N-Oxoammonium salts are also shown to be useful reagents for the metal free 1,2-difunctionalizations of alkenes with heteroatom nucleophiles. While many transformations for the 1,2-addition of heteroatoms to alkenes have been developed, most are dependent on transition metals. Rarer are alkene difunctionalizations that utilize nonmetallic reagents, with most of these reactions relying on photochemical or radical conditions. Investigating these N-oxoammonium salt mediated additions provides a new method for the elaboration of alkenes into molecules with significantly greater complexity. The determination of the stereochemistry of the products of an amino-oxidation with N-oxoammonium salts was also accomplished. Attempts to improve the diastereoselectivity of this process were explored. Investigations have also been initiated to perform these alkene difunctionalizations in an enantioselective manner utilizing anionic phase transfer catalysis. Expansion of the N-oxoammonium salt mediated additions of alkenes with primary alcohols, water, and isatin was also initiated.


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